Extremely drug-resistant TB emerges

Published in The Hindu on September 28, 2006

Mycobacterium - Photo -  CDC
The mutations responsible for XDR-TB are specific for resistance to certain drugs rather than reflecting a fundamental change in the organism’s behaviour. — Photo: CDC

“Drug-resistant TB has frequently been encountered in India and its presence has been known virtually from the time anti-TB drugs were introduced for the treatment of TB,” notes the `TB India 2006′ report of the Ministry of Health and Family Affairs.

Though data on the drug resistance is not available on a national scale, a study carried out by the Tuberculosis Research Centre, Chennai and the Bangalore based National Tuberculosis Institute in eight districts found that 12 per cent of patients on an average were resistant to one of the drugs – isoniazid – used for treating TB. And less than two per cent were found resistant to two vital drugs – isoniazid and rifampicin.

As if detecting and treating multidrug-resistant TB is not challenging enough, the emergence of a new form of multidrug-resistant TB – extremely drug-resistant TB (XTR-TB) – is making TB treatment extremely difficult.

Prohibitive cost

Treating patients who are infected with multidrug-resistant TB (MDR-TB) is still possible though the cost is prohibitive. “The cost of drugs is more than 40 times for treating MDR-TB compared with that for treating patients who harbour sensitive organisms,” Dr. Narayanan highlighted.

Sadly, that is not the case with XDR-TB. “Such tuberculosis [XDR-TB] is virtually untreatable,” according to an editorial in the British Medical Journal (BMJ).

While multidrug-resistant TB arises when the bacteria causing TB is resistant to at least isoniazid and rifampicin, the use of second-line drugs makes it still possible to treat such TB. That is not the case with the extremely drug-resistant TB.

Untreatable

XDR-TB, which is an extreme form of MDR-TB, is resistant to three or more of the six classes of the second-line drugs. “Since WHO guidelines recommend the use of at least four drugs for those with MDR-TB, XDR-TB is untreatable to international standards,” notes an editorial in another journal, Lancet.

It is not just the lack of drugs for treating XDR-TB that is alarming; “… the first drugs in an entirely new class will not be ready for regular use until 2012,” notes a news item in Nature.

Virulent strain

XDR-TB has been found to be very virulent too.

The first outbreak of XDR-TB was seen recently in the KwaZulu-Natal province in South Africa and was reported last month at the XVI International AIDS Conference in Toronto. Of the 53 who tested positive for XDR-TB, 52 died within 25 days of infection. Many of those who died were HIV positive.

The combination is thus deadly – virulent nature of the bacteria, no medicines currently available to fight them, and new drugs to fight them expected to become available only after six more years.

The editorial in the British Medical Journal points out “… the mutations responsible [for XDR-TB] are specific for drug resistance rather than reflecting a fundamental change in behaviour of the organisms.” Hence, XDR-TB “… probably arises fairly regularly and is already disseminated.”

Widespread

It must indeed be true. The outbreak in the KwaZulu-Natal province was not an isolated case. News about 120 patients in 28 hospitals in the KwaZulu-Natal province being infected by XDR-TB emerged during a recent emergency conference in Johannesburg. “Nearly all of those known to be infected are now dead, but many others may be carrying the bacteria,” notes the news item in Nature.

The news items in Nature also quoted Paul Nunn of WHO’s `Stop TB Partnership’ as saying, “There is no systematic survey, so this is just the tip of the iceberg.”

Paul Nunn’s apprehensions may indeed be justified.

“… XDR-TB has been identified in all regions of the world but is most frequent in the countries of the former Soviet Union and in Asia. In the United States, four per cent of MDR-TB cases met the criteria for XDR-TB,” noted WHO. The findings were based on a survey done in 2000-2004 by WHO and the Center for Disease Control and Prevention (CDC) in Atlanta.

Prevalence in India

Information regarding XDR-TB incidence and prevalence in India is currently not available. According to Dr. P.R. Narayanan, Director of Tuberculosis Research Centre (TRC), Chennai, the percentage of MDR-TB cases at TRC, Chennai, who will meet the criteria for being categorised as XDR-TB infected is likely to be less than 2.

Despite the wide prevalence of MDR-TB in many parts of the world, an effective strategy to tackle MDR-TB by WHO is still in a pilot stage.

A national level initiative to tackle drug-resistant TB is just about beginning in India. Currently, only the policy for having laboratory based diagnosis and standardised management for MDR cases with the Directly Observed Treatment, Short-course (DOTS) Plus programme is in place.

The first two centres for undertaking DOTS Plus programme to manage MDR-TB are coming up at Ahmedabad and Nagpur.

If drug resistance was observed from the time anti-TB drugs were introduced, as the `TB India 2006′ report points out, what prevented the government from initiating steps to tackle this much earlier?

According to Dr. Narayanan, treating all patients through DOTS was the priority of the Revised National Tuberculosis Control Programme (RNTCP). And it is now looking at establishing laboratories for testing drug resistant TB.

The DOTS programme was started in 1993. A full-fledged programme was in place in 1997 to increase the detection and cure rate, make medicines always available and make sure that patients complete the treatment.

“We have already achieved 70 per cent detection rate and around 85 per cent cure rate recently with the DOTS programme,” said Dr. Narayanan. “And it has achieved the target set by the Global TB programme.”

Target date

Despite this good news, plans have been drawn up to have estimates of drug resistant TB covering half the population in four years’ time. With the emergence of XDR-TB, the compulsion to revisit the target date cannot be overemphasised.

All the more, as drug resistance is likely to be higher in those people in whom the previous infection had not been treated successfully.

Every day, about 5,000 people develop the disease and around 1,000 die. With the threat of XDR-TB looming large and the number of HIV positive people also going up, the mortality rate is bound to increase exponentially unless some urgent measures are taken up.

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